tbuckley/cabot-search huggingface dataset:
Real-life analysis of pathologic complete response with neoadjuvant trastuzumab plus taxane with or without pertuzumab therapy in HER2 positive locally-advanced breast cancer (HER2PATH Study).
Authors: Ahmet Bilici, Omer Fatih Olmez, Ahmet Sezer, Berna Oksuzoglu, Muhammet Ali Kaplan, Nuri Karadurmus, Erdem Cubukcu, Mehmet A.N. Sendur, Sercan Aksoy, Dilek Erdem, Gul Basaran, Burcu Cakar, Mesut Seker, Cagatay Arslan, Sema Sezgin Goksu, Irfan Cicin, Mahmut Gumus, Fatih Selcukbiricik, Hakan Harputluoglu, Kaan Helvaci
Journal: Journal of Clinical Oncology (2022)

e12610 Background: Studies in HER2+ locally-advanced breast cancer (LABC) patients with neoadjuvant dual HER2 blockage therapy demonstrated high rates of pathologic complete response (pCR). This study evaluates neoadjuvant chemotherapy (NCT) plus trastuzumab (H) with or without pertuzumab (P) therapy with a nation-wide real world setting. Methods: In this study, 1528 female HER2+ LABC patients’ data received NCT plus H with or without P were collected retrospectively from 21 centers. Ethics committee approved the study (NCT04765124). Primary end point was pCR rate (ypT0/Tis ypN0 in the current AJCC staging system). Results: Of the 1528, 951 (62.2%) were received NCT-H, 577 (37.8%) were received NCT-HP, follow-up durations were 30 months and 15 months, median ages were similar between 2 groups (47 years, range: 20-81 and 47 years, range 22-88, respectively). According to the menopausal and hormone receptor status 60% and 53.7% of patients were classified as premenopausal, 56% and 57.8% as estrogen receptor positive and 46.2% and 47.2% as progesterone receptor positive respectively at NCT-HP and NCT-H groups. Despite the patients at NCT-HP group mostly received docetaxel (75%), NCT-H group received weekly paclitaxel (59.4%) as taxane (p&lt;0.001). pCR rate for patients treated with NCT-HP was significantly better than that for patients received NCT-H (66.4% vs. 56.8%, respectively, p&lt;0.001) and there were not any statistical difference according to hormone receptor status. Two-years event-free survival (EFS) rates were 93.5% and 93.2% for NCT-HP and NCT-H groups, respectively (p=0.655), however, two years EFS rate was statistically significant in patients who achieved pCR compared to those who did not achieve pCR (95.1% vs. %90.6, p&lt;0.001). There was not any toxicity leading to death. Conclusions: Our analysis of this real world data shows higher rates of pCR than in clinical trials, also adding pertuzumab to NCT-H demonstrates higher pCR rates and EFS rates compared with NCT-H in patients with HER2+ LABC.
RONC-06. Stereotactic radiosurgery and stereotactic radiotherapy for pediatric brain metastases or recurrences
Authors: Susan McGovern, Dennis Mackin, Jing Li, Arnold Paulino, David Grosshans, Jeffrey Weinberg, David Sandberg, Murali Chintagumpala, Jonathan Gill, Wafik Zaky, Tina Briere, Mary Frances McAleer
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND/PURPOSE: Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) deliver highly conformal, ablative doses of radiation over 1–5 treatments, while minimizing dose to surrounding normal tissues. To document toxicities and outcomes of these treatments in children, our updated institutional experience with SRS or SRT for intracranial targets in pediatric patients was reviewed. METHODS: On an IRB approved study, institutional databases were reviewed to identify pediatric patients with intracranial lesions treated with SRS or SRT from October 2009 to July 2021. Medical records were retrospectively reviewed for patient and treatment characteristics. Outcomes were analyzed for symptomatic radionecrosis and CNS progression. RESULTS: Thirty SRS or SRT treatment courses in 26 patients age 3.2 to 17.8y (median, 15.6y) at the time of SRS or SRT were identified. Twenty-two patients had one treatment and four had two treatments. Sixteen patients had brain metastases from extracranial primary disease; 10 had recurrence of a primary CNS tumor. Fifteen patients had prior fractionated radiation to the brain. Nineteen treatments used Gamma Knife (GK) with Leksell frame, three used GK ICON with mask, and eight used linear accelerator with volumetric modulated arc therapy with thermoplastic mask. All patients (10 treatments in nine patients) treated since July 2016 received mask-based radiation. Twelve of 26 (46%) patients were treated with anesthesia. With 9.6-month median follow up (range, 0.1-96.2m), five patients had progression of treated lesions, eight had distant CNS failure, and one had both local and distant failure, for a crude local failure rate of 6/26 (23%) and a crude distant failure rate of 9/26 (35%). There were no skull fractures or other complications from Leksell frame placement. One patient developed symptomatic radionecrosis requiring surgery. CONCLUSION: SRS and SRT can be safely performed in pediatric patients with intracranial lesions. Mask-based immobilization provides an alternative to frame-based treatments.
CELESTIMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab plus lenalidomide versus rituximab plus lenalidomide in patients with relapsed or refractory follicular lymphoma who have received ≥ 1 line of systemic therapy.
Authors: Loretta J. Nastoupil, Franck Morschhauser, Christian W. Scholz, Mark Bishton, Sung-Soo Yoon, Pratyush Giri, Michael C. Wei, Andrea Knapp, Chi-Chung Li, Alessia Bottos, Haocheng Li, Enkhtsetseg Purev, Nancy L. Bartlett
Journal: Journal of Clinical Oncology (2022)

TPS7588 Background: Despite significant progress with first-line immunochemotherapy, most patients with follicular lymphoma (FL) will eventually relapse with increasing refractoriness and decreasing duration of response to subsequent therapy lines (Rivas-Delgado et al. 2019). Mosunetuzumab (M) is a CD20xCD3 bispecific antibody that engages and redirects T-cells to eliminate malignant B cells (Sun et al. 2015). In an ongoing, pivotal Phase I/II trial of M monotherapy, patients with relapsed/refractory (R/R) FL who have received ≥2 prior treatment lines achieve deep and durable responses (NCT02500407; Budde et al. ASH 2021). Preliminary data from a Phase Ib study have suggested favorable safety and promising activity of M in combination with lenalidomide (Len), a potent immunomodulatory agent that has shown additive/synergistic activity with an anti-CD20 antibody in R/R indolent lymphoma (Leonard et al. 2019), in patients with R/R FL who have received ≥1 prior therapy (NCT04246086; Morschhauser et al. ASH 2021). The chemotherapy-free M-Len combination may represent a promising outpatient therapy option for future management of patients with R/R FL. The randomized, multicenter Phase III study has been initiated. Methods: CELESTIMO (NCT04712097) is a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of M-Len versus rituximab plus Len (R-Len) in patients with previously treated R/R FL. Patients must have histologically documented CD20+ FL (Grades 1–3a) requiring systemic therapy and have received ≥1 prior line of systemic therapy. Patients are randomized (1:1) to receive M-Len (M intravenously [IV] on Days [D] 1, 8 and 15 of Cycle [C] 1 [21-day cycle] and D1 of C2–12 [28-day cycles], plus Len orally [PO] on D1–21 of C2–12) or R-Len (R IV on D1, 8, 15 and 22 of C1 then on D1 of C3, 5, 7, 9, and 11, plus Len PO on D1–21 of C1–12 [all 28-day cycles]), and stratified by disease progression within 24 months of initial treatment (yes/no), number of prior lines of therapy (1 versus ≥2), and refractoriness to anti-CD20 therapy (refractory/non-refractory). The primary endpoint is progression-free survival (PFS) assessed by independent review committee; secondary endpoints include investigator-assessed PFS, complete and objective response, overall survival, and safety. Biomarkers predictive of response to M-Len and R-Len will also be investigated as exploratory endpoints. The study started recruitment in 2021 and plans to enroll ̃400 patients from approximately 16 countries and 150 sites globally. Clinical trial information: NCT04712097.
CD20 and CD19 expression loss in relapsed or refractory b-cell non-Hodgkin lymphoma: A retrospective cohort.
Authors: Joseph Patrick Marshalek, Marcin Dragan, Sarah Tomassetti, Katie LaBarbera, Andy Amaya
Journal: Journal of Clinical Oncology (2022)

e19537 Background: CD20-targeted therapies such as rituximab are widely used in the management of B-cell non-Hodgkin lymphoma (NHL). Re-treatment with anti-CD20 agents is common, however previous research has demonstrated loss of CD20 expression at time of relapse or refractory disease in a subset of patients. There is also amplified interest in alternative targets, specifically CD19, in the relapsed or refractory setting. Incidence of CD19 loss has been explored in post-CAR T cell therapy patients but not described elsewhere. We hypothesized that CD marker loss may be higher than previous reports due to expanded use of CD20- and CD19-targeted therapy. Methods: The present study is a retrospective cohort analysis of 229 patients with B-cell NHL from Harbor-UCLA Medical Center in Los Angeles, CA from 2006 to 2022. Charts were retrospectively reviewed for cases of B-cell NHL, and data was collected about demographics, diagnosis, treatment, and relapses. CD20 and CD19 expression analysis was performed by immunohistochemistry and / or flow cytometry at diagnosis and at each relapse whenever possible. The primary endpoint of the study was the rate of CD marker expression loss at time of relapse. Results: The cohort of 229 patients was composed of 54.1% diffuse large B-cell lymphoma (DLBCL), 14.4% follicular lymphoma (FL), 8.3% high-grade B-cell lymphoma (HGBCL), 7.0% marginal zone lymphoma (MZL), 4.8% mantle cell lymphoma (MCL), and 11.2% other. Overall, 28.8% (66/229) patients had relapsed or refractory disease. The rate of CD20 expression loss was 7.9% (5/63) across all relapses with two patients converting at first relapse (1 FL relapsing as HGBCL, 1 MZL), two patients at 2 nd relapse (1 FL relapsing as DLBCL, 1 MZL relapsing as DLBCL), and one patient at 5 th relapse (1 MZL). All five patients with CD20 phenotypic conversion received rituximab, and three patients received two or more rounds of anti-CD20 therapy. The median OS after CD20 expression loss was 4 months (95% CI 3.3 – 4.7 months). All patients (14/14) who had CD19 testing performed at relapse maintained CD19 positivity. Conclusions: This retrospective study demonstrates a rate of CD20 expression loss at relapse of 7.9%, which is less than previously reported rates ranging between 11-60%. CD20 expression loss seems to be associated with transformation to high-grade lymphoma, poor overall survival, and marginal zone histology. The conservation of CD19 expression across relapses supports the use of novel anti-CD19 targeted therapy in the relapsed or refractory setting. Whenever possible, repeat biopsy should be done at time of relapse prior to treatment with CD-targeted therapy. This study is of notable clinical relevance with expanded use of anti-CD20 agents and novel CD19-targeted therapies in the management of B-cell NHL.
A single cell transcriptional roadmap of human pacemaker cell differentiation
Authors: A Wiesinger, J Li, L Fokkert, P Bakker, A Verkerk, V Christoffels, G Boink, H Devalla
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research council starting grant 714866 and associated proof-of-concept grant 899422 Dutch Heart Foundation Dekker fellowship 2020T023 The sinoatrial node (SAN), the primary pacemaker of the heart generates electrical impulses that set the rhythm of the heartbeat. It is a multicomponent structure composed of "head", "tail" and "transitional" cardiomyocytes as well as proepicardium-derived mesenchymal cells. Previous studies have shown that pacemaker cells of the SAN originate from a common progenitor that also gives rise to the proepicardium. However, little is known of the molecular mechanisms that are implicated in 1) the divergence of pacemaker and proepicardial cells and, 2) the diversification of pacemaker cells into head, tail and transitional cells. Here, we performed single cell RNA sequencing (scRNA-seq) and trajectory inference analysis on human induced pluripotent stem cells (hiPSCs) differentiating to SAN-like cardiomyocytes (SANCM) to construct a roadmap of transcriptional changes and lineage decisions that guide these processes. scRNA-seq of differentiated cells revealed transcriptionally distinct cardiomyocyte populations that closely resemble different subpopulations of the in vivo SAN, such as "head", "tail" and "transitional" cells. Moreover, we identified a side population of proepicardial cells suggesting their shared ontogeny with SANCM, as also reported in vivo. Reconstruction of transcriptional trajectories revealed that the SANCM and proepicardial lineages diverge early on and that this lineage decision is determined by WNT signaling. Furthermore, we uncovered a role for TGFβ and WNT signaling in differentiation towards transitional and head SANCM subtypes, respectively. Manipulation of the identified signaling pathways enhanced gene expression patterns of the corresponding cell type, confirming their involvement in diversification towards SANCM subtypes. Our findings provide new insights into the molecular processes involved in human pacemaker cell differentiation, opening new avenues for complex disease modeling in vitro and inform approaches for cell-therapy based regeneration of the SAN.
Incidence and risk factors for bacterial infection in newly diagnosed multiple myeloma patients undergoing treatment with bortezomib, lenalidomide, and dexamethasone (RVD).
Authors: Matthew James Pianko, Anisa Bici, Victoria Nachar
Journal: Journal of Clinical Oncology (2022)

e20008 Background: Infection is an important cause of morbidity and mortality in newly diagnosed multiple myeloma (NDMM), but the risk of infection using novel treatment regimens is incompletely described in the literature. There are mixed trial results for antibacterial prophylaxis to reduce infection risk in newly diagnosed multiple myeloma and its use remains controversial. Methods: To evaluate the incidence of bacterial infection and early mortality in patients receiving bortezomib, lenalidomide, and dexamethasone (RVD) for NDMM, we performed a retrospective single-center cohort study of patients treated between 01/2014-01/2020. Demographic and clinical data were collected. Two cohorts were generated for those patients with or without bacterial infection during the follow-up period. A multivariate logistic regression was utilized to determine risk factors for bacterial infection. Variables with a P-value &lt;0.2 on univariate analysis were considered for the model. For co-linear variables with a P-value &lt;0.2 on univariate analysis, only one variable was included in the multivariable model. A receiver operating characteristic (ROC) curve was generated to assess the sensitivity and specificity of the model. Results: Of 144 patients, 21 patients (14.5%) experienced a bacterial infection of any grade. 11% of patients received pneumocystis prophylaxis, and 1 patient received levofloxacin prophylaxis. 11 (7.6%) patients experienced grade 3 (G3) or higher infection. One patient died in our cohort; there were no deaths from infection. G3 neutropenia occurred in 11% of patients with 2% experiencing any grade febrile neutropenia. Pneumonia and urinary tract infections were common, affecting 8(5.5%) and 6 (4.2%) patients, respectively. On multivariable analysis (Table), age, smoking history, history of diabetes, antibiotic use in the 60 days preceding 1st cycle of RVD, and high-risk cytogenetics (HR CG) were associated with a greater likelihood of experiencing a bacterial infection. The area under the ROC curve of the multivariable model was 0.829 (95% CI 0.729-0.934). Conclusions: The overall incidence of bacterial infection in NDMM patients receiving induction with RVD was low despite minimal use of antibacterial prophylaxis. Early mortality was uncommon and not attributable to infection. Clinical features may identify a subgroup of patients at greater risk of infection during induction therapy for MM and may impact clinical decisions to utilize antibacterial prophylaxis.[Table: see text]
EPEN-01. Response assessment in pediatric intracranial ependymoma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group
Authors: Holly Lindsay, Maura Massimino, Shivaram Avula, Stavros Stivaros, Richard Grundy, Katie Metrock, Aashim Bhatia, Ana Fernández-Teijeiro, Luisa Chiapparini, Jeffrey Bennett, Karen Wright, Lindsey Hoffman, Amy Smith, Kristian Pajtler, Tina Young Poussaint, Katherine Warren, Nicholas Foreman, David Mirsky
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Ependymomas remain a major cause of cancer-related death in childhood and adolescence, with recurrence occurring in up to 50% of patients. Despite exciting molecular advances in understanding ependymoma tumorigenesis and recurrence, MRI remains the mainstay for assessing objective response to therapy and duration of disease stability. Standardized response assessment criteria for clinical trials studying pediatric intracranial ependymoma are critically needed in order to accurately compare results between studies. METHODS: To generate these standardized response criteria in pediatric intracranial ependymoma, a multidisciplinary team of pediatric neuro-oncologists, neuroradiologists, neurosurgeons, radiation oncologists, and molecular biologists formed the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. The expert members reviewed relevant published literature, assessed current clinical practices, and engaged in iterative discussions to provide consensus recommendations for objective response assessment in pediatric intracranial ependymoma for use in prospective clinical trials. RECOMMENDATIONS AND CONCLUSIONS: The primary sequences for detecting and measuring disease and assessing radiologic response to therapy should be the contrast-enhanced T1-weighted sequence or T2-weighted sequence (T2 or T2-FLAIR) depending on which sequence the tumor is best visualized. When metastatic disease is present, only the three largest lesions will be followed in addition to any residual disease at the primary tumor focus. Importantly, the RAPNO working group notes that radiologic response to therapy is of limited value in clinical trials of patients with ependymoma, since most patients enroll on clinical trials with either no evidence of disease or only minimal disease. In recurrent or progressive disease that cannot be resected, true radiologic disease response to therapy is less clinically meaningful as a study endpoint than event-free and/or overall survival (representing prolonged stable disease) but may provide a signal of efficacy worthy of future exploration in patients with complete to near complete resections.
An open-label, randomized, controlled trial to evaluate the efficacy of antihistamine premedication and infusion prolongation in prevention of hypersensitivity reaction to oxaliplatin.
Authors: Chalita Lagampan, Nattaya Teeyapan, Nattaya Poovorawan, Piyada Sitthideatphaiboon, Napa Parinyanitikul, Chanida Vinayanuwattikun, Virote Sriuranpong, Suebpong Tanasanvimon
Journal: Journal of Clinical Oncology (2022)

12099 Background: Hypersensitivity reaction (HSR) is a common toxicity in patients receiving repeated oxaliplatin. Oxaliplatin induced HSR could be severe and results in treatment discontinuation. There is no standard recommendation for prevention of oxaliplatin induced HSR. Methods: We conducted a prospective, single center, open-label, randomized controlled trial comparing the standard premedication and 2-hour infusion protocol to the additional antihistamine premedication, intravenous chlorpheniramine, and 3-hour infusion protocol. After three months of chemotherapy, the randomization was done at 5 th and 7 th cycles of 3-week and 2-week oxaliplatin based regimens, respectively. The primary endpoint was the incidence of HSR. Results: From July 2020 to March 2021, a total of 160 patients underwent randomization (80 patients in both intervention and control groups). After 11 months follow-up, all patients had completed planned treatment cycles. HSRs occurred in 1 (1.3 %) and 10 (12.5%) patients in intervention and control groups, respectively, p = 0.005). There were 6 (7.5%) patients with more than grade 1 HSRs in control groups, but none in intervention group. In the intervention group, one patient with HSR experienced grade 1 erythema and palpitation. There is no report of significant adverse event from anti-histamine premedication or oxaliplatin infusion prolongation. Conclusions: Additional antihistamine premedication and infusion prolongation started in 2 nd half of treatment course can significantly reduced HSR incidence in patients receiving oxaliplatin. Clinical trial information: TCTR20210506001.
OZM-114: Phase Ib expansion study of CX-5461in patients with solid tumors and <i>BRCA2 </i>and/or <i>PALB2 </i>mutation.
Authors: Husam Alqaisi, Stephanie Lheureux, Michelle McMullen, Jennifer J. Knox, Valerie Bowering, Crystal Lee, Rishi Chinta, Leslie Aguilar, Daniel McCormick, Ariel Chang, Chi-En Huang, Kasia Koziol, John Soong, Diane M. Provencher, Lee S. Rosen, Amit M. Oza
Journal: Journal of Clinical Oncology (2022)

TPS5621 Background: Pre-clinical and clinical data demonstrate that CX-5461 selectively kills HR deficient cancer cells through stabilizing G4 structures and inducing replication-dependent DNA damage. Phase 1 studies suggest CX-5461 has clinical activity and warrants further investigation in HR-deficient tumors, including those with pathogenic BRCA2 and PALB2 mutation. The recommended phase 2 dose (RP2D) requires further refinement to establish the chronic tolerable dose for further phase 2 trials, particularly regarding the incidence of ocular toxicity. The doses of 325mg/m2 and 250mg/m2 were selected for this study expansion cohorts because it is well within the efficacy range and below the first occurrence of ocular toxicity in a previous study. Methods: This is an open-label, multi-center, phase 1b study designed to determine a tolerable dose of CX-5461 in patients with ovarian, pancreatic, prostate, and breast cancers for Phase II trials. Eligible patients will be enrolled into two cohorts: A) Main cohort (target accrual: 32 patients) and B) Exploratory cohorts (target accrual: 20 patients), see table-1 below. The primary outcomes include assessment of: 1) Safety and tolerability of CX-5461, in particular to determine late onset ocular toxicity 2) Anti-tumor activity of CX-5461 in patients with solid tumors and germline BRCA2 and/or PALB2 mutation, and 3) Effect of CX-5461 on Quality of Life measures. Secondary outcomes include evaluation of :1) Safety: CTCAE v 5.0, SAEs, dose modifications due to AEs, 2) Activity: best overall response from tumor evaluations performed every 2 cycles, according to RECIST v1.1, and duration of response., and 3) patient-reported outcomes: PRO (PRO-CTCAE v1.0 questionnaires to evaluate cutaneous, gastrointestinal, visual/perceptual, cardio/circulatory, sleep/wake and miscellaneous symptoms. Exploratory Objectives include assessment of: 1) anti-tumor activity of CX-5461 in patients with ovarian cancer and pathogenic/likely-pathogenic BRCA1 mutation and/or other HRD-associated somatic mutation, and 2) molecular profile of tumors and predictive value of mutational signatures in predicting response or resistance to CX-5461. Clinical trial information: NCT04890613. [Table: see text]
Assessing the effect of red blood cell transfusion on the risk of acute kidney injury after nephron-sparing surgery
Authors: G. Rosiello, F. Cei, G. Fallara, D. Cignoli, G. Basile, G. Colandrea, G. Musso, G. Baiamonte, F. Belladelli, C. Giancristofaro, D. Canibus, I. Rowe, F. Trevisani, A. Bettiga, A. Briganti, R. Bertini, F. Montorsi, A. Salonia, A. Larcher, U. Capitanio
Journal: European Urology (2022)